Multiple myeloma is a cancer similar to leukemia, where immune system cells in the blood begin to multiply out of control.
Newer treatments have shifted from the older types of chemotherapy to newer targeted drugs that have less side effects.
A recent study showed that the combining one of these newest drugs in its class, Kyprolis (carfilzomib), with low doses of steroids was extremely effective in causing multiple myeloma, a plasma cell leukemia, to go into remission.
At a presentation during the American Society of Clinical Oncology’s annual meeting, Andrzej Jakubowiak, MD/PhD, a professor at the University of Chicago showed the latest results from his drug trial, where a majority of patients with multiple myeloma showed no evidence of cancer after treatment.
“Our final results continue to demonstrate the efficacy and safety of carfilzomib when combined with lenalidomide and dexamethasone,” said Dr. Jakubowiak.
“Our data support the potential for CRd as a new frontline treatment option for patients with multiple myeloma with results that are comparable to or better than those achieved with other established frontline regimens followed by high-dose chemotherapy and stem cell transplant.”
The U.S. Food and Drug Administration is currently reviewing Kyprolis for the treatment of relapsed and refractory myeloma.
“Our hope is that our results will provide an effective treatment option for patients with multiple myeloma to help bring us one day closer to curing this deadly disease,” added Dr. Jakubowiak.
The results were from a combined trial for phase I and II that included 53 patients recently diagnosed multiple myeloma. Patients were treated with Kyprolis, Revlimid (lenalidomide), and dexamethasone. The patients in the trial were treated until signs of remission or toxicity were detected.
Out of the 53 patients, 49 were given four 28-day treatment cycles, 67 percent showing a good response. Out of the 53 patients, 45 percent had a complete response to the treatment, with no detectable evidence of cancer at the end of the trial.
More cycles of treatment seemed to be effective, and the group of patients given eight treatment cycles had 80 percent demonstrating a nearly complete response, and 60 percent had no detectable cancer.
In terms of delaying disease progression, the drug was very effective. Progression free survival was 97 percent at 12 months, and 92 percent at 24 months after the trial began.
Side effects reported included slight nerve damage in about 10 percent of patients, immune supression and fatigue in about a third of the patients in the trial. Nerve damage was a concern in the first generation of the drug class, and carfilzomib seems to be successful in minimizing that side effect in comparison to the first generation, Velcade (Bortezomib).
Although the final phase III of the drug’s testing will provide definite proof, researchers concluded that so far the results compare very favorably to current drugs on the market for multiple myeloma.
The U.S. Food and Drug Administration has announced that they will take the trial into consideration for approval starting on July 27, 2012.
According to an article by Bloomberg News, FDA advisory panel chairman Wyndham Wilson, MD/PhD, stated that the side effects were outweighed by the need of patients.
“This is an unmet need in a group that has really run out of options,” Dr. Wilson stated. “There is a pretty convincing signal here that is likely, I believe, to be confirmed in confirmatory trials.”
The study was also published online in the journal Blood June 4, 2012.
Researchers disclosed financial relationships with Celgene, Onyx, Merck, Millennium, Exelixis, Bristol-Myers Squibb and Ortho Biotech.
According to the American Cancer Society, there will be over 21,000 new cases of multiple myeloma in the United States this year. Almost 11,000 people will succumb to the disease. Each person in the United States has an average risk of 1 in 159 of getting the disease during his or her lifetime, making it the second most prevalent blood cancer after non-Hodgkin’s lymphoma.
Multiple myeloma is a type of blood cancer (a hematologic cancer) that affects the plasma cells, a type of white blood cell that is responsible for making the antibodies for the immune system that mark bacteria, viruses, or other cancer cells for destruction and removal from the body. For reference, the different types of leukemia also are hematologic cancers that affect the white blood cells of the immune system.
In multiple myeloma, the cancerous plasma cells grow out of control and collect in the bone marrow, where they form tumors that interfere with the normal production of other blood cells and platelets. Most cases of multiple myeloma also produce a protein called paraprotein, which causes kidney disease as well.
The exact cause of multiple myeloma is unknown, but it likely begins like many other cancers, with one abnormal mutated plasma cell that then divides and produces other cancer cells in greater numbers. The uncontrolled growing plasma cells circulate around the rest of the body and damage multiple tissues. Research has shown an association with multiple myeloma and a genetic abnormality on chromosome 14 in about 50% of patients, and also an abnormality on chromosome 13 in about 50% of patients.
The disease is twice as common in African-Americans than in Caucasians, making it one of the top ten causes of cancer death in the AA population. The peak age of onset is between age 60 and 70, and the disease is more common in men than in women. Additional risk factors include obesity, and having a history of another disease called monoclonal gammopathy of undetermined significance (MGUS, a benign disease where there are paraprotein antibodies in the blood, but they do not cause symptoms or problems).
Initial symptoms of multiple myeloma can vary and affect multiple parts of the body, but the most common symptoms will be anemia (low red blood cell counts, easy bruising and bleeding) and bone pain. The bone pain in multiple myeloma happens because a protein produced activates normal bone cells called osteoclasts, which act to resorb normal bone, causing a ‘punched out’ appearance on bone x-rays. These bones are then more susceptible to fracture, and the bone resorption also causes there to be too much calcium in the blood (hypercalcemia), which can cause weakness, confusion, fatigue, and most importantly kidney failure. Other symptoms include an increased susceptibility to infection and neurological symptoms such as nerve pain, loss of bowel and bladder control, headaches, and retinopathy.
Diagnosis will include blood tests to look for the presence of anemia, the presence of paraprotein, and evidence of kidney problems. A skeletal survey will also be done to look for the presence of bone lesions in the skull, vertebrae, hips and long bones of the extremities. This can be done with X-ray, CT, or MRI. A bone marrow biopsy may be performed to help determine the stage of the disease.
Treatment for multiple myeloma depends on the stage of the disease and how aggressive it is. Some people have such slow growing, asymptomatic disease that treatment may be delayed for years. Other patients will be treated with chemotherapies, most commonly regimens of thalidomide-dexamethasone and bortezomib, or lenalidomide-dexamethasone. Often in relatively healthy patients, chemotherapy is followed by a bone marrow transplant; often from the patient’s own stem cells. Some people can get a bone marrow transplant from another donor, but this is rare. Older patients and sicker patients may not be able to tolerate bone marrow transplant, so these patients may be additionally treated with more chemotherapy.
It is the natural course of the disease for multiple myeloma to relapse after treatment, as chemotherapy and bone marrow transplants will rarely lead to a full cure. Your doctor may choose to try the same treatments again, or try something different to prevent treatment resistance.
Median survival (the midpoint of all patients, not the average) for patients after chemotherapy is 3.5 years, and 4.5 years if they’ve also had a bone marrow transplant. Average survival depends on the other diseases a patient might have, and how aggressive the disease is.